What is ST101?
ST101 is a peptide inhibitor of C/EBPβ, which is a transcription factor overexpressed in many cancers that regulate cellular differentiation and promote tumor survival and proliferation. ST101 significantly decreases the expression of C/EBPβ target genes/proteins involved in cell survival, proliferation and differentiation including BCL-2, MCL-1, BIRC5/survivin, cyclins and ID family of proteins. ST101 has been demonstrated to induce selective cancer cell cytotoxicity across a variety of tumor types, including but not limited to breast cancer, melanoma, prostate cancer, GBM, lung cancer, and AML.
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What is C/EBPβ?
- CCAAT/Enhancer Binding Protein Beta
- Development stage transcription factor expressed but not active in mature cells
- Regulates the expression of genes involved in cell survival, proliferation and differentiation, including Bcl-2 family members, cyclins and ID family genes
- Activation inhibits cellular differentiation and promotes tumor survival and proliferation
- Negative correlation observed between C/EBPβ expression and disease outcomes, e.g., greater C/EBPβ expression is associated with worse clinical outcomes
ST101's Impact on Cancer
C/EBPβ is expressed and active in cancer cells but not active in normal cells (post-differentiation), providing a therapeutic opportunity. By inhibiting the actions of C/EBPβ, ST101 is a tumor-specific treatment that induces tumor cell death by apoptosis and has the potential to sensitize cancer cells to radiation and/or chemotherapy. The impact of ST101 on radiation and chemotherapy sensitivity provides a rationale for combining ST101 with traditional cancer treatment regimens as it advances in clinical development.
Preclinical Data Demonstrates:
- Pharmacokinetic profile with exposures to support once-weekly dosing in the clinic
- Clean safety profile at doses at and above therapeutic levels
- In vivo activity in many models of disease including breast cancer, melanoma, prostate cancer, GBM, lung cancer and AML
- In vitro activity against 3-dimensional patient-derived breast cancer xenograft tumoroids and a panel of cancer lines, including many solid and hematologic tumor types
Initial clinical studies will focus on HRPOS breast cancer, I/O-refractive melanoma, castration-resistant prostate cancer (CRPC), and GBM. Additional oncology indications for which there is already in vivo and/or in vitro data, including AML, will also be pursued.
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